Increasing pregnancy rates

Abstract

The invention relates to a stable formulation for controlling oestrus in a subject. The formulation comprises Gonadotrophin Releasing Hormone or an acceptable salt or analogue thereof, progesterone or an analogue thereof, and an acceptable carrier.

Description

TECHNICAL FIELD[0001]The present invention relates to a formulation for use in increasing the rate of pregnancy in an animal.BACKGROUND OF THE INVENTION[0002]Throughout the dairy industry worldwide, control of the ovulation cycle in cows is essential to ensure a regular supply of lactating cows. Reproductive performance remains an area of dairy management that must be optimised to ensure continued productivity and a sustainable operation. A cow must be pregnant by 85 days postpartum in order to achieve optimum milk production and calve every 12½ months.[0003]Management of reproduction is achieved by treatment of the cows with a variety of hormone interventions at particular times followed by artificial insemination. There are several hormone intervention systems in use throughout the world. Despite the extensive research into these procedures, a disadvantage with them remains that only approximately 50% of the cows receiving these treatments become pregnant. The reasons for this inc...

AI Technical Summary

Benefits of technology

[0045]The formulation may additionally comprise an injection aid. The injection aid may facilitate injection of the formulation (e.g. the GnRH or salt thereof, or the progesterone or analogue thereof) into an animal. The injection aid may comprise an acceptable (e.g. pharmaceutically, veterinarily or clinically acceptable) surfactant. The injection aid may comprise a polymer. It may comprise a hydrophilic polymer. It may be soluble in the carrier and / or in the solvent. It may be pharmaceutically and / or veterinarily and / or clinically acceptable. It may for example comprise polyvinylpyrrolidone (PVP; Plasdone C15; Povidone). Other examples include polyethylene oxide (PEO) and carboxypolymethylene polymers (e.g. carbomer, carbopol, carboxyvinyl polymers). The injection aid may be present in the formulation between about 10 and about 50 mg / ml. The formulation may comprise a preservative, for example an anti-microbial, antibiotic or antioxidant, and may comprise more than one preservative. The preservative may be pharmaceutically and / or veterinarily acceptable. Alternatively it may have no preservative. The preservative may be soluble in the solvent and / or in the carrier. Suitable preservatives include benzyl alcohol, methyl and propyl hydroxybenzoate, chlorocresol, benzalkonium chloride and benzethonium chloride. Suitable antioxidants include butylated hydroxytoluene (BHT), butylated hydroxyanixole (BHA) propyl gallate (PGal), mono and bi-sulfites, ascorbates, cysteine, sulfoxalates, gentistic acid, glutamates, thyoglycolate and thioglycerol and may comprise a combination of two or more antioxidants. The antioxidant should be an acceptable (e.g. pharmaceutically, veterinarily or clinically acceptable) antioxidant. The preservative, e.g. antioxidant, may be present in a concentration effective for preventing microbial growth in the formulation or to prevent deterioration of the formulation. It may be present at between about 0 and 50 mg / ml, for example about 10 mg / ml. The concentration of the preservative may depend on the nature of the preservative. The formulation may be suitable for use in controlling oestrus in an animal. The subject, i.e. the animal, may be a vertebrate, and may be a domestic vertebrate or a farm vertebrate. The animal may be a ruminant, for example a cow or a heifer.

[0299]The present invention also provides a formulation according to the first aspect or made by the process of the third aspect, or a unit dose according to the second aspect or made by the process of the fourth aspect, when used in a hormone intervention programme. The programme may be for increasing the number of animals that become pregnant or for increasing the probability that an animal becomes pregnant. There is also provided the use of GnRH or an acceptable salt or analogue thereof, progesterone or an analogue thereof, and an acceptable solvent for the manufacture of a stable formulation for controlling oestrus in a subject.

Problems solved by technology

Despite the extensive research into these procedures, a disadvantage with them remains that only approximately 50% of the cows receiving these treatments become pregnant.

These feedback systems are complex because the ovaries contain a limited (finite) number of follicles.

However, if circulating progesterone levels are low (e.g. at proestrus), there is a temporary reversal of the negative oestradiol feedback loop and a large surge of LH is released from the pituitary.

In the absence of pregnancy, the combined effect of the lack of ongoing tropism plus the release of prostaglandin by the endometrium results in rapid destruction of the CL and cessation of progesterone production.

The successful implementation of a synchrony programme within a herd is challenging.

Prostaglandin is not effective during the period of the cycle when there is no active CL and it is not effective at destroying a forming CL (the first 5 days after ovulation).

Therefore it seems that DPG synchrony programmes are less effective than originally envisaged in cycling cows.

Failure to do so may contribute to the low success rate of many of those programmes.

This variability places further pressures on any hormone intervention programme.

The differences in cycle lengths make the timing of the artificial insemination extremely difficult in order to fertilise all cows.

It is difficult to heat detect cows at pasture at night, therefore the reduction of the average oestrus duration to less than the period of darkness (12 hours) presents a challenge to artificial mating systems that rely on heat detection within pasture based systems.

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